Structural and functional changes of deep layer pyramidal neurons surrounding microelectrode arrays implanted in rat motor cortex.

Devices capable of recording or stimulating neuronal signals have created new opportunities to understand normal physiology and treat sources of pathology in the brain. However, it is possible that the tissue response to implanted electrodes may influence the nature of the signals detected or stimulated. In this study, we characterized structural and functional changes in deep layer pyramidal neurons surrounding silicon or polyimide-based electrodes implanted in the motor cortex of rats. Devices were captured in 300 µm-thick tissue slices collected at the 1 or 6 week time point post-implantation, and individual neurons were assessed using a combination of whole-cell electrophysiology and 2-photon imaging. We observed disrupted dendritic arbors and a significant reduction in spine densities in neurons surrounding devices. These effects were accompanied by a decrease in the frequency of spontaneous excitatory post-synaptic currents, a reduction in sag amplitude, an increase in spike frequency adaptation, and an increase in filopodia density. We hypothesize that the effects observed in this study may contribute to the signal loss and instability that often accompany chronically implanted electrodes. STATEMENT OF SIGNIFICANCE: Implanted electrodes in the brain can be used to treat sources of pathology and understand normal physiology by recording or stimulating electrical signals generated by local neurons. However, a foreign body response following implantation undermines the performance of these devices. While several studies have investigated the biological mechanisms of device-tissue interactions through histology, transcriptomics, and imaging, our study is the first to directly interrogate effects on the function of neurons surrounding electrodes using single-cell electrophysiology. Additionally, we provide new, detailed assessments of the impacts of electrodes on the dendritic structure and spine morphology of neurons, and we assess effects for both traditional (silicon) and newer polymer electrode materials. These results reveal new potential mechanisms of electrode-tissue interactions.

The 2022 and 2023 Emergency Medicine Residency Match: A Cautionary Tale.

Introduction The emergency medicine (EM) match has undergone significant shifts in 2022 and 2023. While variation in specialty fill rates is expected over time, EM programs noted a significant increase in open positions starting in 2022. Utilizing National Resident Matching Program (NRMP) data over a 10-year period, we identified significant deviations in the emergency medicine match. Methods Shewhart control charts were used to plot the match results over time. A 10-year sample was used to establish the baseline value. From this value, the upper and lower control limits were established. Residency program expansion, decreasing applicant numbers, and changing applicant types were evaluated to detect any non-random changes to the process. Results While the number of EM PGY-1 positions added over time was within the expected range, both the number of unmatched positions and the change in the number of total US MD applicants were outside of this range and are considered to be "out of control." Conclusion It is not yet clear which contributing causes may underlie this sudden change. Several potential etiologies exist, including mismatches in supply and demand for positions, changes in perceptions of the specialty, the effects of COVID-19, and changing workforce needs. Historically similar experiences affecting other specialties, including anesthesia and radiation oncology, are analyzed. Potential solutions for returning to the necessary and usual success of the emergency medicine specialty match are explored.

Congenital Vertebral Malformation in a Neonatal Elk (Cervus canadensis) in Kentucky, USA.

We captured a <1-d-old male elk calf (Cervus canadensis) with a shortened neck. Postmortem examination revealed trauma, meconium aspiration syndrome, and cervical vertebral malformation (partial fusion and narrowed disc spaces). This observation is novel in a wild elk calf, although the gross lesions resembled complex vertebral malformation in neonatal cattle.

Medication-Related Complaints in Residential Aged Care.

Complaints reflect a person's or family's experience within the aged care system and provide important insight into community expectations and consumer priorities. Crucially, when aggregated, complaints data can serve to indicate problematic trends in care provision. Our objective was to characterize the areas of medication management most frequently complained about in Australian residential aged care services from 1 July 2019 to 30 June 2020. A total of 1134 complaint issues specifically referenced medication use. Using content analysis, with a dedicated coding framework, we found that 45% of these complaints related to medicine administration processes. Three categories received nearly two thirds of all complaints: (1) not receiving medication at the right time; (2) inadequate medication management systems; and (3) chemical restraint. Half of the complaints described an indication for use. These were, in order of frequency: 'pain management', 'sedation', and 'infectious disease/infection control'. Only 13% of medication-related complaints referred to a specific pharmacological agent. Opioids were the most common medication class referred to in the complaint dataset, followed by psychotropics and insulin. When compared to complaint data composition overall, a higher proportion of anonymous complaints were made about medication use. Residents were significantly less likely to lodge complaints about medication management, probably due to limited engagement in this part of clinical care provision.

Addressing the educational gap in the role of law enforcement personnel in the resuscitation bay.

BACKGROUND: Health care workers are often uncertain of the role of law enforcement personnel in the resuscitation bay. A cross-sectional, quality improvement project was designed with an educational intervention to address the knowledge gaps. METHODS: There were 2 sessions for trauma surgery and emergency medicine faculty, residents, and staff. The first was a formal presentation by hospital risk management and security focused on answering questions generated by real-life scenarios. After reviewing feedback from the first session, the second session was designed as a panel discussion led by attending physicians who reviewed various clinical scenarios. A pre/postsurvey was administered, including potential clinical scenarios with multiple-choice answers and open feedback. RESULTS: There were 64 presurvey and 31 postsurvey respondents from the first session (48.4%). Significantly more questions were answered correctly from pre to postsurvey (5.5 vs 6.7/16 questions; U = 798.0, P = .048). Of the 14 (45.2%) respondents who provided open-ended feedback, 50% indicated confusion, and 21.4% expressed strong, negative emotions. In the second session, there were 39 presurvey and 18 postsurvey respondents (46.2%). Again, significantly more questions were answered correctly after the second session (2.2 vs 4.5/7 questions; U = 115.0, P ≤ .001). Feedback highlighted that the panel format was considered more helpful than the formal didactic of the first session. CONCLUSION: Confusion about the role of law enforcement personnel in the clinical environment can be partially addressed using multidisciplinary joint conferences that should be led by clinicians to ensure real-life clinical applicability. Further education and law enforcement personnel role clarification for health care workers are critical to protect patient rights.

The role of the angular gyrus in semantic cognition: a synthesis of five functional neuroimaging studies.

Semantic knowledge is central to human cognition. The angular gyrus (AG) is widely considered a key brain region for semantic cognition. However, the role of the AG in semantic processing is controversial. Key controversies concern response polarity (activation vs. deactivation) and its relation to task difficulty, lateralization (left vs. right AG), and functional-anatomical subdivision (PGa vs. PGp subregions). Here, we combined the fMRI data of five studies on semantic processing (n = 172) and analyzed the response profiles from the same anatomical regions-of-interest for left and right PGa and PGp. We found that the AG was consistently deactivated during non-semantic conditions, whereas response polarity during semantic conditions was inconsistent. However, the AG consistently showed relative response differences between semantic and non-semantic conditions, and between different semantic conditions. A combined analysis across all studies revealed that AG responses could be best explained by separable effects of task difficulty and semantic processing demand. Task difficulty effects were stronger in PGa than PGp, regardless of hemisphere. Semantic effects were stronger in left than right AG, regardless of subregion. These results suggest that the AG is engaged in both domain-general task-difficulty-related processes and domain-specific semantic processes. In semantic processing, we propose that left AG acts as a "multimodal convergence zone" that binds different semantic features associated with the same concept, enabling efficient access to task-relevant features.

Age-related reorganization of functional network architecture in semantic cognition.

Cognitive aging is associated with widespread neural reorganization processes in the human brain. However, the behavioral impact of such reorganization is not well understood. The current neuroimaging study investigated age differences in the functional network architecture during semantic word retrieval in young and older adults. Combining task-based functional connectivity, graph theory and cognitive measures of fluid and crystallized intelligence, our findings show age-accompanied large-scale network reorganization even when older adults have intact word retrieval abilities. In particular, functional networks of older adults were characterized by reduced decoupling between systems, reduced segregation and efficiency, and a larger number of hub regions relative to young adults. Exploring the predictive utility of these age-related changes in network topology revealed high, albeit less efficient, performance for older adults whose brain graphs showed stronger dedifferentiation and reduced distinctiveness. Our results extend theoretical accounts on neurocognitive aging by revealing the compensational potential of the commonly reported pattern of network dedifferentiation when older adults can rely on their prior knowledge for successful task processing. However, we also demonstrate the limitations of such compensatory reorganization and show that a youth-like network architecture in terms of balanced integration and segregation is associated with more economical processing.

Detection of Transcranial Alternating Current Stimulation Aftereffects Is Improved by Considering the Individual Electric Field Strength and Self-Rated Sleepiness.

Non-invasive electrical stimulation methods, such as transcranial alternating current stimulation (tACS), are increasingly used in human neuroscience research and offer potential new avenues to treat neurological and psychiatric disorders. However, their often variable effects have also raised concerns in the scientific and clinical communities. This study aims to investigate the influence of subject-specific factors on the alpha tACS-induced aftereffect on the alpha amplitude (measured with electroencephalography, EEG) as well as on the connectivity strength between nodes of the default mode network (DMN) [measured with functional magnetic resonance imaging (fMRI)]. As subject-specific factors we considered the individual electrical field (EFIELD) strength at target regions in the brain, the frequency mismatch between applied stimulation and individual alpha frequency (IAF) and as a covariate, subject's changes in mental state, i.e., sleepiness. Eighteen subjects participated in a tACS and a sham session conducted on different days. Each session consisted of three runs (pre/stimulation/). tACS was applied during the second run at each subject's individual alpha frequency (IAF), applying 1 mA peak-to-peak intensity for 7 min, using an occipital bihemispheric montage. In every run, subjects watched a video designed to increase in-scanner compliance. To investigate the aftereffect of tACS on EEG alpha amplitude and on DMN connectivity strength, EEG data were recorded simultaneously with fMRI data. Self-rated sleepiness was documented using a questionnaire. Conventional statistics (ANOVA) did not show a significant aftereffect of tACS on the alpha amplitude compared to sham stimulation. Including individual EFIELD strengths and self-rated sleepiness scores in a multiple linear regression model, significant tACS-induced aftereffects were observed. However, the subject-wise mismatch between tACS frequency and IAF had no contribution to our model. Neither standard nor extended statistical methods confirmed a tACS-induced aftereffect on DMN functional connectivity. Our results show that it is possible and necessary to disentangle alpha amplitude changes due to intrinsic mechanisms and to external manipulation using tACS on the alpha amplitude that might otherwise be overlooked. Our results suggest that EFIELD is really the most significant factor that explains the alpha amplitude modulation during a tACS session. This knowledge helps to understand the variability of the tACS-induced aftereffects.

Task-specific network interactions across key cognitive domains.

Human cognition is organized in distributed networks in the brain. Although distinct specialized networks have been identified for different cognitive functions, previous work also emphasizes the overlap of key cognitive domains in higher level association areas. The majority of previous studies focused on network overlap and dissociation during resting states whereas task-related network interactions across cognitive domains remain largely unexplored. A better understanding of network overlap and dissociation during different cognitive tasks may elucidate flexible (re-)distribution of resources during human cognition. The present study addresses this issue by providing a broad characterization of large-scale network dynamics in three key cognitive domains. Combining prototypical tasks of the larger domains of attention, language, and social cognition with whole-brain multivariate activity and connectivity approaches, we provide a spatiotemporal characterization of multiple large-scale, overlapping networks that differentially interact across cognitive domains. We show that network activity and interactions increase with increased cognitive complexity across domains. Interaction patterns reveal a common core structure across domains as well as dissociable domain-specific network activity. The observed patterns of activation and deactivation of overlapping and strongly coupled networks provide insight beyond region-specific activity within a particular cognitive domain toward a network perspective approach across diverse key cognitive functions.

The Effects of a Community-Based, Multicomponent, Depression Prevention Intervention in Mothers At-Risk.

The purpose of this study was to develop a 12-week multicomponent, depression prevention pilot intervention and evaluate its feasibility and preliminary effects on improving levels and correlates of depressive symptoms, including anger, self-esteem perceived stress, social support, and racism. A quasi-experimental, mixed-methods design and a community-based participatory research (CBPR) approach was employed. University faculty, students and community residents collaborated at a low-income housing complex in a low-resourced, urban community. Fifteen low-income, ethnic minority mothers ages 23-46 years completed the intervention and evaluation surveys. Eight mothers participated in a focus group. The intervention included social group-dance, health education, and socialization. t-Tests, sign-tests, and thematic analysis was employed. Mothers identified barriers and facilitators of program engagement. Depressive symptoms were significantly reduced (t(14) = 2.41, p = .030). Self-esteem (t(14) = 2.28, p = .039) and social support levels (M = 4.5, p = .035) were significantly increased. This multicomponent intervention is feasible. Preliminary efficacy evidence was mixed.

Setting an agenda to catalyze research in the social and organizational dimensions of Great Lakes remediation, restoration, and revitalization.

The Great Lakes region was once a hub of industry and innovation that provided wealth and identity to the region. Economic upheavals have left the region trying to recreate economies and cleanup degraded environments. There have been multiple, overlapping efforts to change these conditions and create a new narrative for the region through environmental remediation, habitat restoration, and community revitalization on the path towards resilience. The elements that contribute to success are organized differently in different places, and are not always identified or characterized in the environmental literature. Trying to fill this conceptual gap is critical because landscape-scale environmental cleanup has been delivered at the local scale through various partnerships and arrangements. Thus, this special collection of articles in the Journal of Great Lakes Research explores how individuals, organizations, and communities are engaging in the complex process of environmental cleanup and revitalization throughout the region. This collection of articles represents a range of approaches to unpack how people are navigating and contributing to this regenerative process from quantitative studies at the regional scale that characterize global patterns to in-depth qualitative studies that identify and characterize the processes that unfold in specific places to change our environments both ecologically and socially. These articles represent the broad experience unfolding in the region to understand these activities through research and navigate them through practice. This collection will add new dimensions to Great Lakes research by including the individuals, organizations, and agencies as components of the ecosystem.

Community engagement and the importance of partnerships within the Great Lakes Areas of Concern program: A mixed-methods case study.

The Great Lakes Areas of Concern (AOC) program was created through amendments to the Great Lakes Water Quality Agreement (GLWQA) in 1987 to restore contaminated sites using an ecosystem-based approach. This program represents one of the first instances of ecosystem-based management (EBM) in the Great Lakes region with a specific focus on the inclusion of the public and local stakeholders in the process. Despite official language incorporating EBM in the AOC program, implementation of these practices has not been consistent across AOCs given differences in local arrangements of Public Advisory Councils (PACs), approaches to community engagement, and environmental problems. To better understand community engagement in these complex AOCs, this research investigated community, PAC, and state agency perspectives in three AOCs in Michigan: the Kalamazoo River, Saginaw River and Bay, and Rouge River AOCs. We gathered data through interviews, focus groups, and participatory observations with community members, PAC members, and state officials in each AOC. Findings indicate that communities in these areas have minimal connection to the AOC program and PACs. Community members tended to have greater connection to local organizations that provide a variety of opportunities for community members to engage with their environment in ways they value. To better connect the public to the AOC program, PACs may benefit from intentional partnerships with community organizations to increase community engagement. To consistently bolster community engagement in AOCs, we further recommend that state agencies provide additional resources to improve connection to local communities.

Evolving Institutional Arrangements for use of an ecosystem approach in restoring Great Lakes Areas of Concern.

The 1987 Canada-U.S. Great Lakes Water Quality Agreement required Remedial Action Plans (RAPs) be collaboratively generated between local stakeholders and government agencies to implement an ecosystem approach in cleaning up 43 historically polluted Areas of Concern (AOCs) throughout the Laurentian Great Lakes. The institutional arrangements that have emerged over the past 35 years to foster an ecosystem approach in RAPs are expected to have changed over time and be varied in some aspects-reflecting unique socio-ecological contexts of each AOC-while also sharing some characteristics that were either derived from the minimally prescribed framework or developed convergently. Here we surveyed institutional arrangements to describe changes over time relevant to advancing an ecosystem approach in restoring beneficial uses in the 43 AOCs. While eight AOCs evidenced little institutional change, the remaining 35 AOCs demonstrated a growing involvement of local organizations in RAPs, which has enhanced local capacity and ownership and helped strengthen connections to broader watershed initiatives. We also noted an expansion of strategic partnerships that has strengthened science-policy-management linkages and an increasing emphasis on sustainability among RAP institutions. Our study details how institutional arrangements in a decentralized restoration program have evolved to implement an ecosystem approach and address new challenges.

Advancing Translational Research in Environmental Science: The Role and Impact of Social Sciences.

Increasing recognition of the complexity of environmental problems and the need to understand social processes and human values is leading environmental management agencies in many nations, including the USA, to integrate more research from the social sciences through the inclusion of social scientists on interdisciplinary teams. For this study we conducted focus groups at three research laboratories within the U.S. Environmental Protection Agency's Office of Research and Development to better understand how inclusion of social sciences influenced the research process and outcomes, and the barriers to and facilitators of integration. The focus groups identified effects on the research process including improved problem framing, the introduction of new methodologies, and greater stakeholder and public inclusion, while research outcomes included the inclusion or refinement of social and environmental perspectives and systems thinking, increased translatability of research, and new partnerships. Barriers identified included lack of familiarity with social sciences which affected perceptions of social sciences and organizational capacity to absorb and apply social science expertise. Facilitators included receptivity of team members, intentional communication strategies, and project structures and organizational commitment that support interdisciplinary work. Finding a key barrier to be lack of clarity about the different roles social sciences play in translational research, we present a conceptual model defining the roles and contributions of social scientists that clarifies the distinction between "integration" of social sciences in research and "application" of skills and knowledge from the social sciences which play distinct but equally important roles in translational research approaches and solutions-driven research. These insights on the ways social sciences contribute to translational research efforts advance integration of social and natural sciences in environmental science research, particularly in applied contexts.

Differentiation and characterization of neurons derived from rat iPSCs.

BACKGROUND: Induced pluripotent stem cells (iPSCs) may be an advantageous source of neuronal cells to repair damage due to neurological disorders or trauma. Additionally, they are promising candidates to develop models to study underlying mechanisms of neurodegenerative diseases. While successful neural differentiation of iPSCs has been reported in mice, protocols detailing the generation of neural cells from rat iPSCs are relatively limited, and their optimization by manipulating cell culture methods has remained unexplored. NEW METHOD: Here, we describe and compare the effects of four distinct, commonly used substrates on the neuronal differentiation of rat iPSC (riPSC) derived-neural progenitor cells. Our approach is to use substrate coating as a method to enrich differentiated riPSCs for neuronal subtypes with the desired morphology and maturity. We use a combination of electrophysiology, immunofluorescence staining, and Sholl analysis to characterize the cells generated on each substrate over a nine-day time course. RESULTS: The surface coating presented by the cell culture substrate influences the polarity and arborization of differentiating neurons. Polyornithine-laminin coating promoted neuronal arborization and maturation, while Geltrex favored bipolar cells which displayed indicators of functional immaturity. Poly-d-lysine substrate was associated with limited neurite outgrowth and arborization. Gelatin was the least favorable substrate for the growth and differentiation of our cells. Comparison with Existing Method: Rat-derived neural progenitor cells have been previously derived; however, our methods to use substrate coatings to influence morphological and electrical maturity have not been explored previously. CONCLUSION: Substrate coatings can be selected to enrich differentiated riPSCs for distinctive neuronal morphologies.

Aberrant functional connectivity of resting state networks related to misperceptions and intra-individual variability in Parkinson's disease.

Patients with Parkinson's disease (PD) frequently suffer from visual misperceptions and hallucinations, which are difficult to objectify and quantify. We aimed to develop an image recognition task to objectify misperceptions and to assess performance fluctuations in PD patients with and without self-reported hallucinations. Thirty-two non-demented patients with Parkinson's disease (16 with and 16 without self-reported visual hallucinations) and 25 age-matched healthy controls (HC) were tested. Participants performed a dynamic image recognition task with real and scrambled images. We assessed misperception scores and intra-individual variability in recognition times. To gain insight into possible neural mechanisms related to misperceptions and performance fluctuations we correlated resting state network connectivity to the behavioral outcomes in a subsample of Parkinson's disease patients (N = 16). We found that PD patients with self-reported hallucinations (PD-VH) exhibited higher perceptual error rates, due to decreased perceptual sensitivity and not due to changed decision criteria. In addition, PD-VH patients exhibited higher intra-individual variability in recognition times than HC or PD-nonVH patients. Both, misperceptions and intra-individual variability were negatively correlated with resting state functional connectivity involving frontal and parietal brain regions, albeit in partly different subregions. Consistent with previous research suggesting that hallucinations arise from dysfunction in attentional networks, misperception scores correlated with reduced functional connectivity between the dorsal attention and salience network. Intra-individual variability correlated with decreased connectivity between somatomotor and right fronto-parietal networks. We conclude that our task can detect visual misperceptions that are more prevalent in PD-VH patients. In addition, fluctuating visual performance appear to be a signature of PD-VH patients, which might assist further studies of the underlying pathophysiological mechanisms and cognitive processes.

Antibiotic dispensation rates among participants in community-driven health research projects in Arctic Canada.

BACKGROUND: Community-driven projects that aim to address public concerns about health risks from H. pylori infection in Indigenous Arctic communities (estimated H. pylori prevalence = 64%) show frequent failure of treatment to eliminate the bacterium. Among project participants, treatment effectiveness is reduced by antibiotic resistance of infecting H. pylori strains, which in turn, is associated with frequent exposure to antibiotics used to treat other infections. This analysis compares antibiotic dispensation rates in Canadian Arctic communities to rates in urban and rural populations in Alberta, a southern Canadian province. METHODS: Project staff collected antibiotic exposure histories for 297 participants enrolled during 2007-2012 in Aklavik, Tuktoyaktuk, and Fort McPherson in the Northwest Territories, and Old Crow, Yukon. Medical chart reviews collected data on systemic antibiotic dispensations for the 5-year period before enrolment for each participant. Antibiotic dispensation data for urban Edmonton, Alberta (average population ~ 860,000) and rural northern Alberta (average population ~ 450,000) during 2010-2013 were obtained from the Alberta Government Interactive Health Data Application. RESULTS: Antibiotic dispensation rates, estimated as dispensations/person-years (95% confidence interval) were: in Arctic communities, 0.89 (0.84, 0.94); in Edmonton, 0.55 (0.55, 0.56); in rural northern Alberta, 0.63 (0.62, 0.63). Antibiotic dispensation rates were higher in women and older age groups in all regions. In all regions, the highest dispensation rates occurred for ß-lactam and macrolide antibiotic classes. CONCLUSIONS: These results show more frequent antibiotic dispensation in Arctic communities relative to an urban and rural southern Canadian population.

Who Benefits from National Estuaries? Applying the FEGS Classification System to Identify Ecosystem Services and their Beneficiaries.

In spite of their perceived value, the widespread implementation of ecosystem services assessments has been limited because of perceptions of being too technical, too expensive, or requiring special expertise. For example, federal estuary management programs have widely used ecosystem services concepts to frame management issues and communicate with stakeholders. Yet, indicators assessed, monitored, and reported in estuarine management still have traditionally focused on ecological conditions, with weak connections, if any, to social or economic outcomes. Approaches are needed which expand the range of ecosystem services that can be considered, link ecosystem services explicitly to different stakeholder groups, facilitate effective communication with economists and other social scientists, and expand the array of available valuation techniques. We applied the concept of final ecosystem goods and services to review the broad suite of ecosystem services and their beneficiaries relevant to the management of two federal programs for estuary management, the National Estuary Program (NEP) and the National Estuarine Research Reserve System (NERRS). The Final Ecosystem Goods and Services Classification System provided a structured framework for connecting ecosystem services to their beneficiaries and the environments providing them. Document analysis of management plans assessed the degree to which these programs consider ecosystem services, their beneficiaries, and habitats within the estuarine watershed. The hierarchical list of final ecosystem goods and services generated from document analysis serves as a tool for defining management goals, identifying stakeholders, developing meaningful indicators, and conducting valuation studies in estuarine management planning efforts. Though developed here for estuarine management, the keyword hierarchy and final ecosystem goods and services approach have broad applicability and transferability to other environmental management scenarios.